Recycling of The Kidney Anion Exchanger 1 Is Regulated by Adaptor Protein Complex 1B
Bibliographic record
Abstract
Adaptor protein complexes 1 (AP‐1) regulate polarized trafficking of membrane proteins. Here, we investigated the role of AP‐1B in regulating the kidney anion exchanger 1 (kAE1) intracellular trafficking. kAE1 physically interacts with AP‐1B in Madin‐Darby canine kidney cells. We hypothesized that AP‐1B regulates the recycling of endocytosed kAE1 protein and that kAE1 mutants that cause distal renal tubular acidosis, fail to properly interact with AP‐1B. We studied kAE1 WT and a dRTA mutant, kAE1 R901X, which lacks the last 11 amino acids encompassing the potential canonical binding site for AP‐1B. We confirmed the physical interaction between kAE1 and heterologously expressed μ1B subunit of AP‐1B in LLC‐PK1 renal epithelial cells lacking endogenous AP‐1B. A peptide spot assay identified multiple interaction sites of AP‐1B in the kAE1 protein sequence, including residues within the second and sixth cytosolic loops, and the C‐terminus. μ1B heterologous expression decreased the amount of plasma membrane kAE1. Although kAE1 R901X mutant underwent endocytosis slightly faster than kAE1 WT, its recycling rate was decreased compared to kAE1 WT, and was independent from μ1B expression. We also observed that (i) μ1B expression disrupts the interaction of GAPDH with kAE1 WT consistent with both proteins binding to an overlapping site on kAE1, and (ii) phosphorylation of tyrosine 904 within the carboxyl‐terminal interaction motif does not affect the kAE1/AP‐1B interaction. We propose that the apically mis‐targeted kAE1 R901X mutant fails to recycle back to the basolateral membrane due to its inability to properly interact with AP‐1B.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".